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PMID: 12407447 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line.

Neoplasia (New York, N.Y.) ·Vol. 4 ·No. 6 ·2002-00-00 ·Pages 531-8

Lo AW, Sabatier L, Fouladi B, Pottier G, Ricoul M, Murnane JP

Abstract

The development of genomic instability is an important step in generating the multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakage/fusion/bridge (B/F/B) cycle that involves the repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

Keywords
Non-programmatic
MeSH Terms
Anaphase/genetics Blotting, Southern Chromosome Aberrations Chromosome Breakage/genetics Chromosomes, Human, Pair 16/genetics DNA Damage DNA, Neoplasm/genetics Gene Amplification Herpesvirus 1, Human/genetics,metabolism Humans In Situ Hybridization, Fluorescence Karyotyping Plasmids/genetics Telomere/genetics,metabolism Thymidine Kinase/genetics Transfection Tumor Cells, Cultured/physiology Urinary Bladder Neoplasms/genetics
Chemicals
DNA, Neoplasm Thymidine Kinase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lo Anthony W I
Radiation Oncology Research Laboratory, University of California, 1855 Folsom Street, MCB 200, San Francisco, CA 94103, USA.
Sabatier Laure
Fouladi Bijan
Pottier Géraldine
Ricoul Michelle
Murnane John P
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1038/sj.neo.7900267
Published
2002-00-00
Pages
531-8
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1503667
Subset
IM
Grants
NCI NIH HHS · R01 CA069044 · United States
NCI NIH HHS · R01CA69044 · United States
External Links
PubMed source DOI: 10.1038/sj.neo.7900267 PMC Full Text
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